This invention relates to treatments for stroke.
Stroke is a leading cause of death in the United States. The most common type of stroke, focal central nervous system (CNS) ischemia, is characterized by an acute onset of neurological deficit and is primarily caused by the obstruction of an artery to the CNS.
Changes in the level of tissue serotonin [5-hydroxytryptamine] have been shown in experimental models of cerebral ischemia; Welch et al. (1977) Stroke 8, 341-6; Harrison et al. (1979) Stroke 10, 165-8; Jellinger et al. (1978) J. Neurol. Transmission 14, 31-44.
Harrison, et al., (1981) J. Neurol. Neurosurg. Psych. 44, 140-143 investigated the "possible relevance of serotonin changes to the clinical sequelae of cerebral infarction" by measuring the effects of certain serotonin antagonists on neurologic damage in a gerbil stroke model. Eight serotonin antagonists, (5-hydroxy-1-tryptophan, L-tryptophan in conjunction with pargyline, quipazine, methergoline, methysergide, "BW 501C", cyproheptidine, and p-chloro-phenylalanine) were typically administered intravenously at doses ranging from 1 mg/Kg to 150 mg/Kg 1 hr. prior to induced cerebral infarction; p-chloro-phenylalanine was administered 24-48 hrs. after infarction at a dosage of 300 mg/Kg. Harrison et al. says that serotonin "receptor antagonists . . . failed to produce a striking change in the prevalence of neurological morbidity."